The University of Texas M. D. Anderson Cancer Center (MDACC) is a free-standing comprehensive cancer center within the University of Texas system. The mission of the MDACC is to eliminate cancer in Texas, the nation and the world through outstanding integrated programs of patient care, research, education and prevention. MDACC is dedicated wholly to the study of cancer involving a continuum of basic, clinical and population-based investigation, with an emphasis on multidisciplinary translational research. During the last 5 years, the number of cancer center members has increased 35%, facilities including those under construction have increased 39% and new patients have increased 70%. Annual citations in Pub Med have increased to 1179 (9.4%), including many articles in journals with the highest impact factors, reflecting substantial contributions to cancer research. During the last 4 years, total grant funding has increased 39%. NCI grant support has increased from $79M to $118M (49%) with the largest number of NCI grants for any center (more than 240), including 10 SPOREs and 11 P01s. Research Programs remain at 19 with three additional programs in development. Since the last CCSG renewal, basic science has been strengthened substantially in immunology, signaling, genetics, non-mammalian models and structural biology, to complement traditional strengths in carcinogenesis, metastasis and developmental biology. Translational research has been enhanced at each organ site, a program initiated in molecular diagnostics and new leaders and faculty recruited in molecular imaging and targeted therapy. In-house drug development has been encouraged with more than 30 drugs and agents in different stages of development. Clinical research has been strengthened with the recruitment of new leadership, further development of infrastructure and data bases, initiation of an institution-wide phase I program and emphasis on hypothesis driven, investigator initiated trials. Clinical trials conducted at MDACC have prompted the approval of six new drugs and antibodies by the FDA. Strategic alliances have been established selectively with major pharmaceutical companies to accelerate the pace of drug development. Cancer prevention has continued to flourish with development of new methods in behavioral research, a major epidemiologic study in the Hispanic community of Houston, a program in health disparities research and the completion of major trials in chemoprevention. Support is requested for 21 shared resources that have facilitated these many activities and enhanced our research productivity. Funds are also requested for Planning and Evaluation, Senior Leaders, Program Leaders and for Development to enhance faculty recruitment, to provide seed support for multi-investigator grants and to develop a limited number of new shared resources. This support will be critical for MDACC's efforts to Make Cancer History.